Hepatocellular carcinoma: pathogenesis

Usually the tumor is white, sometimes colored with bile and can contain foci of hemorrhage and necrosis. Large intrahepatic branches of portal and hepatic veins are often thrombosed and contain tumor masses. There are 3 forms of hepatocellular carcinoma: expansive (or nodular - in the form of large nodes with clear boundaries), massive (or infiltrative) and multifocal (or diffuse). With the nodular form of hepatocellular carcinoma, it often develops in the liver, which is not affected by cirrhosis; while in Japan there are encapsulated tumors. In the West and in African countries, in most cases of hepatocellular carcinoma is a massive and diffuse forms.

Hepatocellular carcinoma

Cells resemble normal hepatocytes and are located in the form of compact finger-shaped processes or solid trabeculae. The similarity of a tumor with a normal hepatic tissue can be expressed in varying degrees. Tumor cells sometimes secrete bile and contain glycogen. The intercellular stroma is absent, and the tumor cells lining the blood-filled spaces.

Tumor cells are usually smaller than normal hepatocytes; they have a polygonal shape and a granular cytoplasm. Sometimes there are atypical giant cells. The cytoplasm is usually eosinophilic, with an increase in the degree of malignancy, it becomes basophilic. The nuclei are hyperchromic, of different sizes. Sometimes there are mainly eosinophilic tumors. In the center of the tumor, foci of necrosis are often noted. An early indication is the infiltration of periportal lymph vessels with tumor cells. In approximately 15% of patients, usually with a high concentration of a-PF in the serum, PIC-positive diastasis-resistant globular inclusions, which can be hepatocyte-produced glycoproteins, are detected.

In the tumor, alpha ₁ -antitrypsin and a-fetoprotein are also often detected .

By the degree of malignancy, liver tumors can correspond to the entire range - from benign regeneration units to malignant tumors. Dysplasia of hepatocytes occupies an intermediate position. The probability of malignization is especially high in the presence of dysplastic hepatocytes of small size. An increase in the density of the nuclei of tumor cells is 1.3 times or more in comparison with the density of the nuclei of normal hepatocytes, indicating a highly differentiated hepatocellular carcinoma.

Electron microscopy data. In the cytoplasm of human hepatocellular carcinoma cells, hyaline is contained. The cytoplasmic inclusions include filaments and autophagic vacuoles.

Clear cell hepatocellular carcinoma

Tumor cells with this form of hepatocellular carcinoma have a non-staining, often foamy cytoplasm. In a large volume of the cytoplasm, lipids, and sometimes glycogen, are found. The tumor is often accompanied by hypoglycemia and hypercholesterolemia; the forecast may be different.

Hepatocellular carcinoma with giant cells

With this rare form of hepatocellular carcinoma, clusters of giant cells resembling osteoclasts that are surrounded by mononuclear cells are detected in some tumor sites. In other areas, the tumor has a histological pattern typical for hepatocellular carcinoma.

Tumor spreading

Intrahepatic. Metastases can affect the entire liver or be limited to one lobe. Metastasis usually occurs by hematogenesis, since tumor cells are adjacent to vascular spaces. It is also possible to lymphogenous metastases and sprouting directly into healthy tissue.

Extrahepatic. The tumor can sprout into small and large branches of portal and hepatic veins, as well as into a hollow vein. Metastases of hepatocellular carcinoma can also be detected in the esophageal varicose veins, even if they are sclerotized. This is the way metastasis can occur in the lungs. These metastases usually have small dimensions. Tumor emboli can lead to thrombosis of the pulmonary arteries. Systemic spread can lead to the appearance of metastases in any part of the body, especially in the bones. Often, regional lymph nodes are damaged in the gates of the liver, as well as chains of lymph nodes of the mediastinum and neck.

The defeat of the peritoneal tumor leads to hemorrhagic ascites. This complication can be a sign of the terminal stage of the disease.

Histological signs of metastases. Metastases resemble a primary tumor in structure, and even signs of bile formation can be detected. However, sometimes the cells of the primary tumor and metastases can vary significantly. The presence of bile or glycogen in metastatic cells indicates that the primary tumor has hepatic origin.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]